2008 Research Report: Heart Centre (Cardiology/ABMU)

Director: Prof Anthony M Dart BA DPhil BM BCh FRACP FRCP FAHA

Research studies conducted within the department of Cardiovascular Medicine range from identification of the best strategies for reducing the risk of cardiovascular disease through to the evaluation of the latest technological advances. Throughout this spectrum studies also range from those tackling basic mechanisms through to practical therapeutics. Studies within the department commonly rely on collaborations with other Alfred departments or AMREP partners, most notably the Baker IDI Research Institute. In addition to investigator led studies the department also participates in a number of multi-centred trials.

Coronary artery disease is responsible for a major component of the clinical work of the department and a number projects are ongoing in this area. These include an investigator led single centre study into whether the early administration of the agent deferrioxamine can reduce the size of a heart attack. This agent binds iron and is postulated to limit the size of a heart effect through limiting the damage done by oxidation products. This is the first large single centre study on infarct size to be conducted within the department and is led by Prof Stephen Duffy. Other studies are investigating the pattern of blood flow in diseased and disease free coronary arteries using the new methodologies of wave intensity measurement. These studies build on previous extensive experience on the biomechanical properties of arteries (Prof Dart and A/Prof B Kingwell). The department is a major contributor and supporter to the Melbourne Intervention Group register of outcomes following angioplasty.

The second major clinical area for the department consists of heart failure and transplantation and a number of projects are currently active in this area. These include studies to try to limit the cardiac fibrosis which occurs in transplant patients. Other studies are examining the phenomenon of heart failure with preserved systolic pump function which is known to be widely prevalent but ill understood. Research in heart failure within the department is co-ordinated by Prof David Kaye. A number of studies are evaluating devices in relation to heart failure, hypertension and valvular heart disease. These include the implantation of a device to measure the early onset of heart failure, a percutaneous technique to reduce inappropriate nerve activity to the kidney which is a cause for high blood pressure and a new technique to replace diseased aortic valves without an operation (percutaneous aortic valve replacement). These studies are led within the department by Dr Tony Walton. In addition the department is evaluating a device developed by Prof David Kaye to reduce the damage done by contrast dye in patients with impaired kidney function who are undergoing coronary angiography.

Non-invasive cardiovascular imaging is a major activity of the department and has expanded from echocardiography to cardiac MRI and, in conjunction with the department of Radiology, the use of CT coronary angiography. Studies in cardiac MRI, led by Dr Andrew Taylor, have particularly focused on ways of assessing scar damage within the heart in patients with heart failure and after a heart attack. These studies will help not only to explain the presence of heart failure in some patients but also guide the appropriate use of therapeutic strategies, such as biventricular pacing and automatic implantable cardiac defibrillators.

A number of studies, particularly in conjunction with colleagues at the Baker IDI, are investigating the metabolic basis for blood vessel disease, particularly in relation to glucose and lipids. A number of investigations have concentrated on functions of HDL (good) cholesterol. A major study completed during the year, and led by Dr James Shaw, demonstrated that a single infusion of HDL cholesterol could favourably modify properties of atheroma. This may open the way for such therapeutic measures to be used in the treatment of unstable coronary syndrome. Other studies led by A/Prof Bronwyn Kingwell and Prof Stephen Duffy, demonstrated major effects of HDL on other metabolic processes such as inflammation and also a role for HDL in glucose metabolism. Several studies have been commenced with obesity and lipid disorders. These have included effects of obesity and its treatment on endothelial progenitor cells (Dr Jaye Chin-Dusting, Prof Dart) a major mechanism of vascular repair and a novel dietary treatment for elevated cholesterol (Dr Michael Skilton).

Studies in the field of arrhythmias have concentrated on atrial fibrillation which continues to grow as a clinical problem. The particular emphasis in studies in this field within the department is on the relation between atrial fibrillation and heart failure and whether restoration of normal rhythm would result in less morbidity from cardiac disease. The introduction into the department of advanced mapping techniques has made possible studies dependent on the ability to undertake (pulmonary vein isolation) ablation therapy for atrial fibrillation. Research in this area is led by Dr Peter Kistler.

A number of studies are investigating the antecedents of cardiovascular disease particularly including studies on brain-heart interaction led by Prof Murray Esler. Considerable attention in recent years has been given to the links between illnesses such as depression and panic attacks and cardiac, particularly coronary events. The work by Prof Esler and his team seeks to unravel some of the mechanisms by which these occur, with a particular focus on the role of the sympathetic nervous system.

A number of major findings from the department have been published in 2008:

  • A single infusion of reconstitution of HDL (good) cholesterol can produce beneficial changes in the composition and character of atherosclerotic plaque (Shaw et al Circ Res. 2008;103:1084-91).
  • Cardiac MRI is able to identify fibrosis within the heart (Taylor et al. JACC. 2008;52:1574-80).
  • Circulating p-selectin is elevated in patients with atherosclerosis and exerts important effects on cell adhesion in relation to vascular pathophysiology (Woollard et al. Circ Res. 2008:103:1128-38).
  • Kidney failure is a common complication of heart failure and its cause remains poorly understood. This study showed that high venous pressures, as might be caused by tricuspid valve failure, were a major determinant of kidney dysfunction. This provides a new target for treatment in this disorder. (Kaye et al. J Cardiac Fail. 2008:14:824-30).
  • For patients with end stage heart failure, options are limited. Heart transplantation is not possible in many patients for a variety of reasons. Prof Kaye's team have been investigating how recent advances in the basic science of gene therapy could be potentially transferred to the clinic. This study describes a new method for gene therapy to the heart in large animals. (Kaye et al. Gene Ther. 2008:15:1550-7).

Other Achievements (Awards/Prizes/Major Grants)

Ahimastos A: NHF Grant-in-Aid Award (Senior Investigator) ACE inhibition; A potential therapy for peripheral arterial disease. 2008-2010.
Ahimastos A: Short-listed for the "Clinical Science Young Investigator Award" at European Society of Cardiology, Munich August 2008; 800 Euro Prize.
Chin-Dusting J: NHMRC Project Grant (#526664). The role of arginase in peripheral occlusive arterial disease. (2009-2011: $234, 250).
Chin-Dusting J/Dart A: Nanovic Victoria Pty Ltd. Investigator-led seeding grant. Targeted imaging of vasculature using nanoparticles. (2007-2009: $278,000).
Dart A/Esler M/Kaye D/Jennings G/ Kingwell B/Chin-Dusting J are CI's on a NHMRC Program Grant (#472600). A program of research addressing the transition from health to advanced cardiovascular disease. (2008-2012: $12,281,756).
Dart A: Invited speaker Gaston Bauer Lecture, Cardiac Society of Australia and New Zealand, Adelaide 2008.
de Courten B: Inflammation and Obesity Stock conference, Cairns.
Drew B: Australian Diabetes Society, "Pincus Taft Young Investigator Award".
Drew B: International Vascular Biology meeting – Melbourne Satellite, "Best Poster Presentation".
Taylor A: NHF Grant-in-Aid. Cardiac magnetic resonance imaging in the evaluation of myocardial fibrosis in advanced heart failure. (2 yrs $123,500).
Vaddadi G: Won the Ralph Reader Prize (clinical) at the Cardiac Society of Australia and New Zealand, Adelaide 2008.
Woollard K: Obtained a NHF Fellowship (2009-2010).

Completed PhD's

Murphy A. PhD, Monash University. 'Soluble mediators of monocyte activation.'
Rose H: PhD, Monash University. 'Impact of HIV infection and its treatment on cholesterol metabolism.'
White A. PhD, Monash University. 'Large artery stiffness as a risk marker and therapeutic target: Structural and genetic aspects.'

Current Students

Bertovic D: PhD, Monash University. 'Cardiovascular hemodynamics in health and disease.' NHF; Postgraduate Medical Research Scholarship: expected completion 2010.
Butler M: PhD, Monash University. 'Novel imaging modalities for detection of organ fibrosis.' Australian Postgraduate Award (APA) scholarship: 2009-2010.
Chan W. PhD, Monash University. 'Iron and oxidative stress in coronary artery disease.' NHMRC Medical Postgraduate Scholarship. 2008-2010.
Elsik M: PhD, Monash University. 'Myocardial fibrosis and cardiac remodelling in CHF – novel treatments and monitoring strategies.' Expected completion 2009.
Iles L. PhD, Monash University. 'Myocardial fibrosis and heart failure.' Expected completion date 2012.
Khong S: PhD, Monash University. 'The role of arginase II in cardiovascular pathology.' Postgraduate scholarship: expected completion 2010.
Lee S: PhD, Monash University. 'Omega-3 fatty acids and recovery from cardiovascular risk.' Departmental funds: expected completion 2010.
Mukherjee S. PhD, Monash University. 'Nitric Oxide and oxidative stress in human hypertension.'
Vaddadi G: PhD, Monash University. 'Sympathetic neurobiology of recurrent syncope.' NHMRC/NHF scholarship: 2006-2009.

Current/Ongoing Trials

Hs-CRP and its association with vascular events in HIV positive patients. (CI: Dart)

Soluble P-selectin levels in peripheral arterial occlusive disease (POAD). (CI's: Woollard, Chin, Dart)

Cardiovascular disease and its genetic correlation with pseudoxanthoma elasticum. (CI: Dart)

Metabolic regulation of ABCA1 expression in patients with type 2 diabetes and athletes. (CI: Kingwell)

In vivo microdialysis studies of metabolite and neurotransmitter overflow from the adipose tissue and skeletal. (CI: Esler)

Clinical follow up of Patients undergoing percutaneous revascularization at Melbourne hospitals. (CI: Duffy)

Does systemic arterial compliance predicts blood pressure responses in patients undergoing percutaneous. (CI: Shaw)

Effect of fitness on chronic low-grade activation of the immune system and insulin sensitivity in physically fit and healthy sedentary individuals. (CI: Kingwell)

Effects of polymorphisms in antioxidant genes on the clinical presentation (stable versus unstable coronary syndrome) in a group of patients undergoing coronary angiography. (CI: Duffy)

A novel mechanism mediating anti-atherosclerotic and metabolic actions of HDL cholesterol. (CI: Kingwell)

A Randomised Dose Ranging Study of Hexadecasaccharide including Active Control in Patients with Unstable Angina or Non-ST-segment elevation Myocardial Infarction Scheduled to Undergo Percutaneous Coronary Intervention (SHINE). (CI: Shaw)

Sex dimorphism in MMP activity in peripheral white blood cells from healthy controls and patients with acute myocardial infarction. (CI: Dart)

Growth factor secretion by the normal and failing human heart. (CI: Kaye)

Identifying predictors of progressive mitral regurgitation in heart failure. (CI: Kaye/Mariani)

Role of sP-selectin in Patients with peripheral occlusive arterial disease. (CI: Chin-Dusting)

Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease. (CI: Dart)

Heart Transplant Myocardial fibrosis Study: Effect of Spironolactone on Myocardial fibrosis and myocardial function in patients with left ventricular diastolic dysfunction after heart transplantation. (CI: Leet)

A clinical trial comparing cangrelor to clopidogrel in subjects who require percutaneous coronary intervention. (CI: Duffy)

Endothelial progenitor cell number and function in congenital vascular malformation. (CI: Dart)

Mechanisms of the disorders of circulatory control which may cause syncope: Pure Autonomic Failure, multiple systems atrophy and Parkinson's disease with autonomic failure. (CI: Esler)

Sympathetic nervous system activation in renal failure. Its contribution to pathogenesis and progression. (CI: Lambert)

Examining cognitive function in patients with the postural orthostatic tachycardia syndrome (POTS). (CI: Lambert)

IMPROVE IT. A Multicenter, Double-Blind, Randomised Study to Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting With Acute Coronary Syndrome (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial). (CI: Shaw)

Mechanisms of the disorders of circulatory control which may cause syncope: Neurocardiogenic Syncope and Carotid Sinus Hypersensitivity. (CI: Esler)

Role of Endothelial progenitor cells in metabolic syndrome and weight loss. (CI: Dart)

Do High Dose Tirofiban and Reopro have Similar Effects on Platelet Function and Recovery of LV function in Patients With Acute Myocardial Infarction? (CI: Shaw)

Sympathetic function in the heart, brain and kidney of patients with postural orthostatic tachycardia syndrome. (CI: Esler)

ACE Inhibition; A Potential New Therapy for Peripheral Arterial Disease. (CI: Kingwell)

Novel therapies for the treatment of Type 2 Diabetes. (CI: Kingwell)

Mechanisms of sympathetic overactivity in the metabolic syndrome: effects of reversing insulin resistance by drug treatment. (CI: Straznicky)

The use of single chain antibodies for the detection of monocyte activation in patients with stable and acute coronary syndromes. (CI: Karlheinz)

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-0974 in Healthy Male Japanese Subjects. (CI: Masuo)

Lipid profiling: early detection, monitoring and pathogenesis of atherosclerotic heart disease. (CI: Meikle)

The Atrial Electrical and Structural Effects of Systemic and Pulmonary Hypertension in Humans. (CI: Kistler)

Characterization of electrophysiological and radiological substrates in ischemic and dilated cardiomyopathy patients with and without ventricular tachycardia using three-dimensional electroanatomic mapping and magnetic resonance imaging. (CI: Kaye)

Randomised controlled pilot trial of n-acetylcysteine in the management of chronic heart failure with coexistent chronic renal failure. (CI: Kaye)

A randomised crossover trial to assess the impact of the dietary n-6:n-3 polyunsaturated fatty acid ratio on markers of cardiovascular health in patients with dyslipidaemia. (CI: Chin-Dusting)

Native Kidney Denervation in Patients with End Stage Renal Disease. (CI: Schlaich)

The influence of heart rate reduction upon central arterial pressure in younger and older healthy individuals. (CI: Kingwell)

Characterization of electrophysiological, radiological and histological substrates for ventricular tachycardia in patients undergoing cardiac transplantation for ischemic and non-ischemic cardiomyopathy. (CI: Kaye)

The influence of heart rate reduction upon coronary blood flow as assessed by coronary wave intensity analysis. (CI: Kingwell)

Determination of central arterial pressure and left ventricular ejection fraction in humans by analysis of peripheral arterial pressure waveforms. (CI: Kingwell)

Cardiac magnetic resonance imaging in the evaluation of myocardial fibrosis in advanced heart failure. (CI: Iles)

Reversibility of chronic atrial remodeling late after curative atrial flutter ablation. (CI: Kistler)

A randomised study of a Nurse-led Intervention for Less Chronic Heart Failure: The NIL-CHF Study. (CI: Stewart)

A multicentre, randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of SCH 530348 in addition to standard of care in subjects with acute coronary syndrome. (CI: Duffy)

The role of the Renin Angiotensin Aldosterone system activation in myocardial fibrosis, diastolic function and its link to liver fibrosis in morbid obesity. (CI: Wong)

A Single Center Pilot Study Evaluating the Use of the Osprey Medical CIN SystemTM. (CI: Duffy)

Noradrenaline transporter (NET) dysfunction in neural circulatory disorders. (CI: Schlaich)

Understanding the acute effects of prolonged sedentary behaviour (sitting) on post-meal glucose and lipids – A pilot study. (CI: Kingwell)

Cardiac and Liver Fibrosis in Patients with the Metabolic Syndrome as detected by Magnetic Resonance T1 mapping. (CI: Butler)

Role of the sympathetic nervous system in obesity and associated metabolic abnormalities in the early development of organ damage in young adults. (CI: Lambert)

Do coronary plaque biomechanical differences between diabetic and non diabetic subjects relate to differences in plaque morphology and measures of neovascularisation. (CI: Shaw)

A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Tolerability and Efficacy of Anacetrapib When Added to Ongoing Therapy With a Statin in Patients With Hypercholesterolemia or Mixed Hyperlipidemia. (CI: Nestel)

Exertional dyspnea in patients with echocardiographic signs of diastolic dysfunction: are symptoms really caused by impaired left ventricular filling? – A prospective case-control study. (CI: Kaye)

Effects of Peri-procedural Iron Chelation on Myocardial Infarct Size and Oxidative Stress In ST-elevation Myocardial Infarction. (CI: Duffy)

Does tricuspid regurgitation contribute to renal dysfunction in patients with heart failure? (CI: Kaye)

Utilisation of coronary CT angiography (CCTA) in cardiac risk stratification. (CI: Taylor)

INTERNATIONAL ReValving™ REGISTRY. (CI: Walton)

Cardiac and liver fibrosis in patients with viral hepatitis as detected by Magnetic Resonance T1 mapping. (CI: Taylor)

Anaemia and myocardial iron in heart failure. (CI: Kaye)

Applying Novel Biomarkers to Assess Cardiac Risk in Patients Undergoing Major Vascular Surgery: Defining Iron, Oxidative Stress, Inflammation, Matrix Metalloproteinases, Coagulation Factors, Lipidomics, Endothelial Dysfunction, and Other Relevant Risk Mar. (CI: Duffy)

Correlation of cardiac magnetic resonance imaging (CMR) findings with subsequent ventricular arrhythmias in subjects with heart failure. (CI: Taylor)

A Quality Improvement Initiative on the Discharge Management of Acute Coronary Syndromes (DMACS). (CI: Dart)

The role of cardiac magnetic resonance imaging and serum biomarkers in the identification and monitoring of myocardial involvement in patients with established non-cardiac sarcoidosis. (CI: Habersberger)

Effects of a 10 or 15 mg single intravenous bolus of ivabradine versus placebo on heart rate control during a multislice computed tomography coronary angiography for the evaluation of coronary artery disease. A randomised, double-blind, international multicentre study. (CI: Taylor)

A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Withdrawal-Design Study to Assess the Clinical Effect of Droxidopa in Subjects With Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Neuropathy and symptomatic Neurogenic Orthostatic Hypotension. (CI: Esler)

Time to transfusion study. (CI: Phillips)

The influence of dairy on risk and progression of obesity and metabolic syndrome: An Ausdiab Prospective study. (CI's: Shaw/Meikle)

Does Warfarin alter diastolic function? (CI: Kaye)

Publications

  1. Ahimastos AA, Dart AM, Kingwell BA. Angiotensin II blockade in Marfan's syndrome. N Engl J Med 2008;359(16):1732.
  2. Ahimastos AA, Dart AM, Lawler A, Blombery PA, Kingwell BA. Reduced arterial stiffness may contribute to angiotensin-converting enzyme inhibitor induced improvements in walking time in peripheral arterial disease patients. J Hypertens 2008;26(5):1037-42.
  3. Ajani AE, Reid CM, Duffy SJ, Andrianopoulos N, Lefkovits J, Black A, New G, Lew R, Shaw JA, Yan BP, Gurvitch R, Al-Fiadh A, Brennan AL, Clark DJ. Outcomes after percutaneous coronary intervention in contemporary Australian practice: insights from a large multicentre registry. Med J Aust 2008;189(8):423-8.
  4. Balasubramaniam R, Kistler PM. AF and heart failure: the chicken or the egg? Heart 2008;Jul 16 [Epub ahead of print].
  5. Ballinger ML, Osman N, Wilks AF, Su S, Burns CJ, Bu X, Little PJ. Pyrido-pyrimidine derivative CYC10424 inhibits glycosaminoglycan changes on vascular smooth muscle-derived proteoglycans and reduces lipoprotein binding. J Cardiovasc Pharmacol 2008;52(5):403-12.
  6. Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C, Socratous F, Hastings J, Guo L, Wiesner G, Kaye DM, Bayles R, Schlaich MP, Lambert GW. Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatr 2008;65(1):38-46.
  7. Baumert M, Lambert GW, Dawood T, Lambert EA, Esler MD, McGrane M, Barton D, Nalivaiko E. QT interval variability and cardiac norepinephrine spillover in patients with depression and panic disorder. Am J Physiol Heart Circ Physiol 2008;295(3):H962-H968.
  8. Bayles RG, Dawood T, Lambert EA, Schlaich MP, Lambert GW. Elevated cardiac risk in patients with major depressive disorder. Am J Psychiatry 2008;165(1):137.
  9. Bayliss J, Maguire JA, Bailey M, Leet A, Kaye D, Richardson M, Bergin PJ, Dowling J, Thomson NM, Stein AN. Increased vascular endothelial growth factor mRNA in endomyocardial biopsies from allografts demonstrating severe acute rejection: a
  10. Byrne M, Kaye DM, Power J. The synergism between atrial fibrillation and heart failure. J Card Fail 2008;14(4):320-6.
  11. Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM. Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Ther 2008;15(23):1550-7.
  12. Camuglia A, Manins V, Taylor A, Hengel C. Case report and review: epicardial coronary artery fibromuscular dysplasia. Heart Lung Circ 2008;Jan 30 [Epub ahead of print].
  13. Chung J, Nguyen AK, Henstridge DC, Holmes AG, Chan MH, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy SJ, Horvath I, Mestril R, Watt MJ, Hooper PL, Kingwell BA, Vigh L, Hevener A, Febbraio MA. HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci USA 2008;105(5):1739-44.
  14. Dart AM, Cameron JD, Gatzka C, Kingwell BA, Jennings GLR. Letter. Response to effects of angiotensin-converting enzyme inhibitors on central blood pressure. Hypertension 2008;50(3):e64.
  15. Dart AM, Kingwell BA, Gatzka CD, Willson K, Liang YL, Berry KL, Wing LM, Reid CM, Ryan P, Beilin LJ, Jennings GL, Johnston CI, McNeil JJ, MacDonald GJ, Morgan TO, West MJ, Cameron JD. Smaller aortic dimensions do not fully account for the greater pulse pressure in elderly female hypertensives. Hypertension 2008;51(4):1129-34.
  16. Duffy SJ, Dart AM. Novel cardiac therapies and innocent by standers. Lancet 2008;371(9626):1726-8.
  17. Esler M, Eikelis N, Schlaich M, Lambert G, Alvarenga M, Dawood T, Kaye D, Barton D, Pier C, Guo L, Brenchley C, Jennings G, Lambert E. Chronic mental stress is a cause of essential hypertension: presence of biological markers of stress. Clin Exp Pharmacol Physiol 2008;35(4):498-502.
  18. Esler MD, Eikelis N, Lambert E, Straznicky N. Neural mechanisms and management of obesity-related hypertension. Curr Cardiol Rep 2008;10(6):456-63.
  19. Fang L, Gao XM, Samuel CS, Su Y, Lim YL, Dart AM, Du XJ. Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction. Clin Sci 2008;115(3):99-106.
  20. Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R. The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 2008;51(16):1581-7.
  21. Gould PA, Esler MD, Kaye DM. Atrial fibrillation is associated with decreased cardiac sympathetic response to isometric exercise in CHF in comparison to sinus
  22. Haqqani HM, Kalman JM, Kistler PM. Catheter ablation for atrial fibrillation: have we come the full circle? J Cardiovasc Electrophysiol 2008;19(5):480-2.
  23. Hoang A, Tefft C, Duffy SJ, Formosa M, Henstridge DC, Kingwell BA, Sviridov D. ABCA1 expression in humans is associated with physical activity and alcohol consumption. Atherosclerosis 2008;197(1):197-203.
  24. Iles L, Pfluger H, Phrommintikul A, Cherayath J, Aksit P, Gupta SN, Kaye DM, Taylor AJ. Evaluation of diffuse myocardial fibrosis in heart failure with cardiac magnetic resonance contrast-enhanced T1 mapping. J Am Coll Cardiol 2008;52(19):1574-80.
  25. Kaye DM, Esler MD. Autonomic control of the aging heart. Neuromolecular Med 2008;10(3):179-86.
  26. Kaye DM, Esler MD. Re: Cardiac denervation does/does not play a major role in exercise limitation after heart transplantation. J Appl Physiol 2008;104(2):567.
  27. Kaye DM, Hoshijima M, Chien KR. Reversing advanced heart failure by targeting Ca2+ cycling. Annu Rev Med 2008;59:13-28.
  28. Kiriazis H, Wang K, Xu Q, Gao XM, Ming Z, Su Y, Moore XL, Lambert G, Gibbs ME, Dart AM, Du XJ. Knockout of β(1)- and β(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis. Br J Pharmacol 2008;153(4):684-92.
  29. Kistler PM. Multi electrode ablation for paroxysmal atrial fibrillation: Pulmonary vein isolation made easy? Heart Rhythm 2008;5(12):1643-44.
  30. Kistler PM, Rajappan K, Harris S, Earley MJ, Richmond L, Sporton SC, Schilling RJ. Impact of image integration on catheter ablation of atrial fibrillation using electroanatomic mapping: a prospective randomized study. Eur Heart J 2008;29(24):3029-36.
  31. Lambert E, Dawood T, Schlaich M, Straznicky N, Esler M, Lambert G. Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk. Clin Exp Pharmacol Physiol 2008;35(4):503-7.
  32. Lambert E, Eikelis N, Esler M, Dawood T, Schlaich M, Bayles R, Socratous F, Agrotis A, Jennings G, Lambert G, Vaddadi G. Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with the postural tachycardia syndrome. Circ Arrhythmia Electrophysiol 2008;1:103-109.
  33. Maeder MT, Holst DP, Kaye DM. Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure. J Card Fail 2008;14(10):824-30.
  34. Maeder MT, Kaye DM. B-type natriuretic peptide in end-stage renal disease: a neurohormone rather than a volume status monitor. South Med J 2008;101(11):1081-2.
  35. Masuo K, Lambert GW, Esler MD. Does epinephrine cause hypertension? - Epinephrine hypothesis. In: Lawson AG, Gorman RI (eds). Research Progress on Epinephrine, Nova Science Publishers, New York 2008;Chapter 5:95-114.
  36. Masuo K, Lambert GW, Rakugi H, Ogihara T, Esler MD. Neurovascular role of sympathetic nervous system and β- adrenoceptor polymorphisms in obesity and hypertension. Curr Hypertens Rev 2008;4(2):121-30.
  37. Masuo K, Straznicky N, Esler MD. Obesity and obesity-related hypertension: role of the sympathetic nervous system and β-adrenoreceptor polymorphisms. In: Kaneko M (ed) Sympathetic Nervous System Research Developments, Nova Science Publishers, USA 2008;Chapter 2:67-92.
  38. Masuo K, Straznicky NE, Lambert GW, Katsuya T, Sugimoto K, Rakugi H, Socratous F, Hastings J, Lambert EA, Ogihara T, Esler MD. Leptin-receptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic nerve activation in a Caucasian male population. Hypertens Res 2008;31(6):1093-100.
  39. Pfluger HB, Phrommintikul A, Mariani JA, Cherayath JG, Taylor AJ. Utility of myocardial fibrosis and fatty infiltration detected by cardiac magnetic resonance imaging in the diagnosis of arrhythmogenic right ventricular dysplasia-a single centre experience. Heart Lung Circ 2008;17(6):478-83.
  40. Roberts-Thomson KC, Stevenson IH, Kistler PM, Haqqani HM, Goldblatt JC, Sanders P, Kalman JM. Anatomically determined functional conduction delay in the posterior left atrium relationship to structural heart disease. J Am Coll Cardiol 2008;51(8):856-62.
  41. Rose H, Hoy J, Woolley I, Tchoua U, Bukrinsky M, Dart A, Sviridov D. HIV infection and high density lipoprotein metabolism. Atherosclerosis 2008;199(1):79-86.
  42. Shaw JA, Andrianopoulos N, Duffy S, Walton AS, Clark D, Lew R, Sebastian M, New G, Brennan A, Reid C, Ajani AE; On behalf of the Melbourne Interventional Group. Renal impairment is an independent predictor of adverse events post coronary intervention in patients with and without drug-eluting stents. Cardiovasc Revasc Med 2008;9(4):218-223.
  43. Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S, Sviridov D, Dart AM. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res 2008;103(10):1084-91.
  44. Straznicky NE, Eikelis N, Lambert EA, Esler MD. Mediators of sympathetic activation in metabolic syndrome obesity. Curr Hypertens Rep 2008;10(6):440-7.
  45. Straznicky NE, Nestel PJ, Esler MD. Autonomic nervous control of metabolic function. In: Squire LR (ed) Encyclopaedia of Neuroscience. Elsevier, Academic Press 2008.
  46. Sviridov D, Hoang A, Ooi E, Watts G, Barrett PH, Nestel P. Indices of reverse cholesterol transport in subjects with metabolic syndrome after treatment with rosuvastatin. Atherosclerosis 2008;197(2):732-9.
  47. Woodcock EA, Kistler PM, Ju Y. Phosphoinositide signalling and cardiac arrhythmias. Cardiovasc Res 2008;Nov 11 [Epub ahead of print].
  48. Woollard KJ, Suhartoyo A, Harris EE, Eisenhardt SU, Jackson SP, Peter K, Dart AM, Hickey MJ, Chin-Dusting JP. Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation. Circ Res 2008;103(10):1128-38.
  49. Xu Q, Lekgabe ED, Gao XM, Ming Z, Tregear GW, Dart AM, Bathgate RA, Samuel CS, Du XJ. Endogenous relaxin does not affect chronic pressure overload-induced cardiac hypertrophy and fibrosis. Endocrinology 2008;149(2):476-82.
  50. Yan BP, Ajani AE, New G, Duffy SJ, Farouque O, Shaw J, Sebastian M, Lew R, Brennan A, Andrianopoulos N, Reid C, Clark DJ; Melbourne Interventional Group Investigators. Are drug-eluting stents indicated in large coronary arteries? Insights from a multi-centre percutaneous coronary intervention registry. Int J Cardiol 2008;130(3):374-9.
  51. Yan BP, Duffy SJ, Clark DJ, Lefkovits J, Warren R, Gurvitch R, Lew R, Sebastian M, Brennan A, Andrianopoulos N, Reid CM, Ajani AE; Melbourne Interventional Group. Rates of stent thrombosis in bare-metal versus drug-eluting stents (from a large Australian multicenter registry). Am J Cardiol 2008;101(12):1716-22.
  52. Zhang WZ, Venardos K, Finch S, Kaye DM. Detrimental effect of oxidized LDL on endothelial arginine metabolism and transportation. Int J Biochem Cell Biol 2008;40(5):920-8.

Translational Research

Several of the projects within the department of Cardiovascular Medicine translate the findings of biomedical research and development into clinical practice. Three studies undertaken during the past year illustrate different aspects of the translational process. Studies from Dr James Shaw and colleagues have demonstrated that the infusion of HDL (good) cholesterol can reduce inflammation in atherosclerotic plaque given several days prior to plaque removal by percutaneous atherectomy. These studies paved the way for future investigations of the effects of such therapy on clinical end-points. Studies by Prof Esler and Dr Tony Walton have demonstrated that interrupting the sympathetic nervous supply of the kidneys in subjects with high blood pressure can be done safely through a percutaneous catheter and appears to result in worthwhile gains in blood pressure reduction in subjects who are poorly controlled with medical therapy. These studies have been accepted for publication in the Lancet and again will form the basis for a definitive clinical trial to establish the place of this novel therapy. Third example relates to the study within the department of an innovation developed by Prof David Kaye to make it possible to more safely undertake coronary angiography in subjects with renal failure. The research builds on Prof Kaye's long experience with similar techniques in both clinical and experimental animal research and uses a catheter based device to extract radio-opaque dye used in cardiac angiography before it has circulated through the body and potentially caused further kidney damage.

CoreValve

The CoreValve ReValving System consists of a porcine pericardial bioprosthetic valve mounted and sutured in a multi-level self-expanding Nitinol frame. The bioprosthesis is housed in a collapsed position for percutaneous delivery via a catheter-based technique, and implanted within the diseased aortic valve. The procedure is performed utilizing local anaesthesia (with or without conscious sedation).

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